The goals of this research project are to further investigate our preliminary findings that 2% dimethyl sulfoxide (DMSO) in the drinking water of rabbits partially inhibited the development of dietary-cholesterol induced atherosclerosis despite the presence of severe hypercholesterolemia. In vitro studies were performed to more clearly define the effects of DMSO and its major metabolic product, dimethyl sulfone (DMSO2) on cell growth, cholesterol uptake and connective tissue protein synthesis by cultured vascular smooth muscle cells, endothelial cells and skin fibroblasts. Both DMSO and DMSO2 were found to inhibit the growth and proliferation of vascular smooth muscle and endothelial cells at concentrations of 1% or greater. However, the growth inhibitory effects of these compounds were totally or partially reversible up to concentrations of 3%. At concentrations of greater than 3% these compounds were toxic to the cells, usually resulting in cell death after 1-2 days exposure. DMSO was also found to significantly lower the accumulation of cholesterol esters by cultured fibroblasts exposed to high concentrations of low density lipoproteins (LDL). The effect of 2% DMSO in the culture medium was to reduce the binding, internalization and degradation of LDL by about 30%. Finally, DMSO was found to inhibit collage synthesis by 25-30%. This decreased collagen synthesis could be accounted for by an exclusive reduction in the synthesis of type I collagen; the synthesis of type III collagen remained relatively unchanged.